Rockfield Stephanie M, Turnis Meghan E, Rodriguez-Enriquez Ricardo, Bathina Madhavi, Ng Seng Kah, Kurtz Nathan, Becerra Mora Nathalie, Pelletier Stephane, Robinson Camenzind G, Vogel Peter, Opferman Joseph T
Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Electron Microscopy, Department of Cellular Imaging Shared Resources, St. Jude Children's Research Hospital, Memphis, TN, USA.
Life Sci Alliance. 2024 Mar 11;7(6). doi: 10.26508/lsa.202302329. Print 2024 Jun.
The mitochondrial contact site and cristae organizing system (MICOS) is important for crista junction formation and for maintaining inner mitochondrial membrane architecture. A key component of the MICOS complex is MIC60, which has been well studied in yeast and cell culture models. However, only one recent study has demonstrated the embryonic lethality of losing (the gene encoding MIC60) expression. Tamoxifen-inducible ROSA-CreER-mediated deletion of in adult mice disrupted the MICOS complex, increased mitochondria size, altered cristae morphology, and was lethal within 12 d. Pathologically, these mice displayed defective intestinal muscle function (paralytic ileus) culminating in dehydration. We also identified bone marrow (BM) hypocellularity in -deleted mice, although BM transplants from wild-type mice did not improve survival. Altogether, this inducible mouse model demonstrates the importance of MIC60 in vivo, in both hematopoietic and non-hematopoietic tissues, and provides a valuable resource for future mechanistic investigations into the MICOS complex.
线粒体接触位点与嵴组织系统（MICOS）对于嵴连接的形成以及维持线粒体内膜结构至关重要。MICOS复合物的一个关键组分是MIC60，它在酵母和细胞培养模型中已得到充分研究。然而，最近仅有一项研究证明缺失（编码MIC60的基因）表达会导致胚胎致死。他莫昔芬诱导的ROSA-CreER介导的成年小鼠体内缺失会破坏MICOS复合物，增加线粒体大小，改变嵴形态，并在12天内致死。病理上，这些小鼠表现出肠道肌肉功能缺陷（麻痹性肠梗阻），最终导致脱水。我们还在缺失的小鼠中发现了骨髓细胞减少，尽管来自野生型小鼠的骨髓移植并未改善存活率。总之，这种诱导性小鼠模型证明了MIC60在体内造血组织和非造血组织中的重要性，并为未来对MICOS复合物的机制研究提供了宝贵资源。
